Why whales are big but not bigger: Physiological drivers and ecological limits in the age of ocean giants.

The largest animals are marine filter feeders, but the underlying mechanism of their large size remains unexplained. We measured feeding performance and prey quality to demonstrate how whale gigantism is driven by the interplay of prey abundance and harvesting mechanisms that increase prey capture rates and energy intake. The foraging efficiency of toothed whales that feed on single prey is constrained by the abundance of large prey, whereas filter-feeding baleen whales seasonally exploit vast swarms of small prey at high efficiencies. Given temporally and spatially aggregated prey, filter feeding provides an evolutionary pathway to extremes in body size that are not available to lineages that must feed on one prey at a time. Maximum size in filter feeders is likely constrained by prey availability across space and time.

Extreme bradycardia and tachycardia in the world's largest animal.

The biology of the blue whale has long fascinated physiologists because of the animal's extreme size. Despite high energetic demands from a large body, low mass-specific metabolic rates are likely powered by low heart rates. Diving bradycardia should slow blood oxygen depletion and enhance dive time available for foraging at depth. However, blue whales exhibit a high-cost feeding mechanism, lunge feeding, whereby large volumes of prey-laden water are intermittently engulfed and filtered during dives. This paradox of such a large, slowly beating heart and the high cost of lunge feeding represents a unique test of our understanding of cardiac function, hemodynamics, and physiological limits to body size. Here, we used an electrocardiogram (ECG)-depth recorder tag to measure blue whale heart rates during foraging dives as deep as 184 m and as long as 16.5 min. Heart rates during dives were typically 4 to 8 beats min-1 (bpm) and as low as 2 bpm, while after-dive surface heart rates were 25 to 37 bpm, near the estimated maximum heart rate possible. Despite extreme bradycardia, we recorded a 2.5-fold increase above diving heart rate minima during the powered ascent phase of feeding lunges followed by a gradual decrease of heart rate during the prolonged glide as engulfed water is filtered. These heart rate dynamics explain the unique hemodynamic design in rorqual whales consisting of a large-diameter, highly compliant, elastic aortic arch that allows the aorta to accommodate blood ejected by the heart and maintain blood flow during the long and variable pauses between heartbeats.

The role of environmental factors in search and rescue incidents in Nunavut, Canada.

OBJECTIVES: Unintentional injury is a leading cause of morbidity and mortality in Nunavut, where the importance of land-based activities and reliance on semi-permanent trails create unique risk profiles. Climate change is believed to be exacerbating these risks, although no studies have quantitatively examined links between environmental conditions and injury and distress in the Canadian Arctic. We examine the correlation between environmental conditions and land-based search and rescue (SAR) incidents across Nunavut. STUDY DESIGN: Case study. METHODS: Case data were acquired from the Canadian National Search and Rescue Secretariat. Gasoline sales from across the territory are then used to model land-use and exposure. We compare weather and ice conditions during 202 SAR incidents to conditions during 755 non-SAR days (controls) between 2013 and 2014. RESULTS: We show daily ambient temperature, ice concentration, ice thickness, and variation in types of ice to be correlated with SAR rates across the territory during the study period. CONCLUSIONS: These conditions are projected to be affected by future climate change, which could increase demand for SAR and increase injury rates in the absence of targeted efforts aimed at prevention and treatment. This study provides health practitioners and public health communities with clearer understanding to prepare, respond to, and prevent injuries across the Arctic.

Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures.

BACKGROUND: Currently, there are no published randomized controlled trials evaluating the efficacy and safety of adjunctive antiepileptic therapy in idiopathic generalized epilepsy with myoclonic seizures. METHODS: This randomized, double-blind, placebo-controlled multicenter trial assessed the efficacy and tolerability of adjunctive treatment with levetiracetam 3,000 mg/day in adolescents (>or=12 years) and adults (or=8 days during a prospective 8-week baseline period, despite antiepileptic monotherapy. The 8-week baseline period was followed by 4-week up-titration, 12-week evaluation, and 6-week down-titration/conversion periods. RESULTS: Of 122 patients randomized, 120 (levetiracetam, n = 60; placebo, n = 60) were evaluable. Diagnoses were either juvenile myoclonic epilepsy (93.4%) or juvenile absence epilepsy (6.6%). A reduction of >or=50% in the number of days/week with myoclonic seizures was seen in 58.3% of patients in the levetiracetam group and in 23.3% of patients in the placebo group (p < 0.001) during the treatment period. Levetiracetam-treated patients were more likely to respond to treatment than patients receiving placebo (OR = 4.77; 95% CI, 2.12 to 10.77; p < 0.001). Levetiracetam-treated patients had higher freedom from myoclonic seizures (25.0% vs 5.0%; p = 0.004) and all seizure types (21.7% vs 1.7%; p < 0.001) during the evaluation period. The only adverse events more frequent with levetiracetam were somnolence and neck pain. CONCLUSION: These results suggest that levetiracetam is an effective and well-tolerated adjunctive treatment for patients with previously uncontrolled idiopathic generalized epilepsy with myoclonic seizures.

Residual capacitive coupling and the measurement of permittivity in magnetic induction tomography.

In an ideal magnetic induction tomography (MIT) system, the coupling between the coils and the sample is entirely by the magnetic field. In a practical system, unwanted electric-field (capacitive) coupling can also exist and cause large errors in the MIT measurements unless the hardware is designed carefully. A series of tests was carried out to assess the magnitude of capacitive coupling present in a 10 MHz MIT system designed for biomedical use and other applications involving low-conductivity samples (

Determining the background levels of bismuth in tissues of wild game birds: a first step in addressing the environmental consequences of using bismuth shotshells.

Bismuth shotshells have been approved as a "nontoxic" alternative to lead in North America. Approval was based on a limited number of studies; even background levels of bismuth in wildfowl were unknown. We report on the concentration of bismuth (and lead) in muscle and liver tissues of wildfowl (Anas platyrhynchos, Anas acuta, Anas crecca, Branta canadensis, Chen caerulescens) harvested with lead shotshell. Average liver-bismuth levels detected in the present study (e.g., teal, 0.05 microg/g dw; mallard, 0.09 microg/g dw) suggest analytical error in other studies examining the effects of bismuth in birds. Significant positive relationships between bismuth- and lead-tissue levels for muscle when all species were combined (and for B. canadensis and C. caerulescens separately) can be explained by noting that bismuth is a contaminant of lead. Thus, more research is recommended to confirm the appropriateness of bismuth as a "nontoxic" shot alternative.

A primary field compensation scheme for planar array magnetic induction tomography.

In biomedical magnetic induction tomography (MIT), measurement precision may be improved by incorporating some form of primary field compensation/cancellation scheme. Schemes which have been described previously include gradiometric approaches and the use of 'back-off' coils. In each of these methods, however, the primary field cancellation was achieved only for a single transmitter/receiver combination. For the purpose of imaging, it would be desirable for a fully electronically scanned MIT system to provide a complete set of measurements, all with the primary field cancelled. A single channel suitable for incorporation into an MIT system with planar-array geometry is described. The transmitter is a 6-turn coil of wire 5 cm in diameter. The receiver is a surface mount inductor, of inductance 10 microH, mounted such that, in principle, no net primary field flux threads it. The results of measurements carried out with the single channel system suggest that the signal due to the primary excitation field can be reduced on average by a factor of 298 by the sensor geometry over the operating frequency range 1-10 MHz. The standard deviation and drift of the signal with the system adjusted for maximum primary field cancellation, expressed as a percentage of the signal when the receiver coil was rotated until its axis of sensitivity lay along the primary field, were 0.0009% and 0.009%, respectively. The filter time constant used was 30 ms.

Circuit for the measurement of small phase delays in MIT.

A single-channel MIT measuring system for obtaining phase delays is given. The circuit, which is described in detail, uses a high-frequency analogue multiplier to measure the phase difference between the signal and a reference signal. The noise in the phase measurement is approximately 1.5 millidegree when the time constant of measuring is 0.1 s, and the drift over about 1 day is approximately 10 millidegree.

Magnetic induction tomography: phase versus vector-voltmeter measurement techniques.

In magnetic induction tomography (MIT) the in-quadrature component, and hence the phase, of the received signal contains information about the conductivity of the tissue. The quality of imaging will depend on the precision with which phase can be measured. Preliminary studies suggest that a precision of 10 m degrees may be required for a practical biomedical MIT system operating at 10 MHz. This paper describes the results of measurements carried out with a 16-channel, downconverting, 10 MHz, MIT system utilizing two types of data extraction techniques: direct-phase measurement and measurement of the in-phase and in-quadrature components of the signal with a vector voltmeter. The basic precision provided by each technique was 50 m degrees, with thermal drift representing the major limiting factor. Preliminary measurements of average conductivity and permittivity for a human thigh in vivo are given.

Frequency downconversion and phase noise in MIT.

High-frequency (3-30 MHz) operation of MIT systems offers advantages in terms of the larger induced signal amplitudes compared to systems operating in the low- or medium-frequency ranges. Signal distribution at HF, however, presents difficulties, in particular with isolation and phase stability. It is therefore valuable to translate received signals to a lower frequency range through heterodyne downconversion, a process in which relative signal amplitude and phase information is in theory retained. Measurement of signal amplitude and phase is also simplified at lower frequencies. The paper presents details of measurements on a direct phase measurement system utilizing heterodyne downconversion and compares the relative performance of three circuit configurations. The 100-sample average precision of a circuit suitable for use as a receiver within an MIT system was 0.008 degrees for input amplitude -21 dBV. As the input amplitude was reduced from -21 to -72 dBV variation in the measured phase offset was observed, with the offset varying by 1.8 degrees. The precision of the circuit deteriorated with decreasing input amplitude, but was found to provide a 100-sample average precision of <0.022 degrees down to an input amplitude of -60 dBV. The characteristics of phase noise within the system are discussed.

Testing the validity of a critical sulfur and nitrogen load model in southern Ontario, Canada, using soil chemistry data from MARYP.

The validity of a steady-state mass balance model (Arp et al., 1996; referred to as ARP) was tested using physicochemical soil data from the Monitoring Acid Rain Youth Program (MARYP). Four ARP sites were matched with ten MARYP sites according to proximity, bedrock type and subsoil pH to test the validity of the ARP model for critical load exceedances. Soil solution pH, base concentration and A1 concentration from MARYP sites, which were well matched to ARP sites, validated the modelled critical load exceedances. Higher exceedance areas were associated with more acidic pH and lower base and higher A1 concentrations from matched MARYP sites and vice versa. One ARP site was inappropriately matched with MARYP sites and could not be validated using base and A1 concentrations. This study also confirmed the southern limit of the zero critical load exceedance isopleth from the model. However, variability of the other exceedance isopleths was noted due to the limited number of sites used in the model. The validation of these sites in the ARP model and the zero critical load exceedance isopleth nonetheless allows greater confidence in using this model as a management tool for acidic deposition.

Further characterization of human microsomal 3alpha-hydroxysteroid dehydrogenase.

This manuscript reports further characterization of the recently discovered human short-chain alcohol dehydrogenase, proposed to oxidize 3alpha-androstanediol to dihydrotestosterone in testis and prostate (M. G. Biswas and D. W. Russell, 1997, J. Biol. Chem. 272, 15959-15966). Enzyme expressed using the Baculovirus System localized in the microsomal fraction and catalyzed oxidation and reduction of the functional groups on steroids at carbons 3 and 17. Autoradiography assays revealed that the enzyme was most efficient as a 3alpha-hydroxysteroid oxidoreductase. High affinity of the enzyme for NADH (Km of 0.18 microM), lack of stereospecificity in the reductive direction, and poor efficiency for 3beta- versus 3alpha-hydroxyl oxidation could account for the observed transient accumulation of 3beta-stereoisomers in the oxidative reaction. Consistent with the 65% sequence identity with RoDH dehydrogenases, the enzyme oxidized all-trans-retinol with the Km value of 3.2 microM and Vmax value of 1.2 nmol/min per milligram microsomes. 13-cis-Retinol and all-trans-retinol bound to the cellular retinol-binding protein were not substrates. Neurosteroid allopregnanolone was a better substrate than all-trans-retinol with the Km and Vmax values of 0.24 microM and 14.7 nmol/min per milligram microsomes. Northern blot analysis revealed that the corresponding mRNA was present in adult human brain (caudate nucleus, amygdala, hippocampus, substantia nigra, thalamus) and spinal cord in addition to other tissues. The message was also detected in fetal lung, liver, and brain. Antibodies against the enzyme recognized a protein of approximately 35 kDa in the particulate fraction of human tissues. This study presents new information about enzymatic properties, substrate specificity, and tissue distribution of this enzyme, and provides a better insight into its possible physiological function(s).

Characterization of a novel type of human microsomal 3alpha -hydroxysteroid dehydrogenase: unique tissue distribution and catalytic properties.

We report characterization of a novel member of the short chain dehydrogenase/reductase superfamily. The 1513-base pair cDNA encodes a 319-amino acid protein. The corresponding gene spans over 26 kilobase pairs on chromosome 2 and contains five exons. The recombinant protein produced using the baculovirus system is localized in the microsomal fraction of Sf9 cells and is an integral membrane protein with cytosolic orientation of its catalytic domain. The enzyme exhibits an oxidoreductase activity toward hydroxysteroids with NAD(+) and NADH as the preferred cofactors. The enzyme is most efficient as a 3alpha-hydroxysteroid dehydrogenase, converting 3alpha-tetrahydroprogesterone (allopregnanolone) to dihydroprogesterone and 3alpha-androstanediol to dihydrotestosterone with similar catalytic efficiency (V(max) values of 13-14 nmol/min/mg microsomal protein and K(m) values of 5-7 microm). Despite approximately 44-47% sequence identity with retinol/3alpha-hydroxysterol dehydrogenases, the enzyme is not active toward retinols. The corresponding message is abundant in human trachea and is present at lower levels in the spinal cord, bone marrow, brain, heart, colon, testis, placenta, lung, and lymph node. Thus, the new short chain dehydrogenase represents a novel type of microsomal NAD(+)-dependent 3alpha-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution.

Cloning of the human RoDH-related short chain dehydrogenase gene and analysis of its structure.

We have previously characterized the first human NAD(+)-dependent short chain dehydrogenase capable of oxidizing all-trans-retinol and androgens, and found only in the liver and skin. In a search for related human enzymes, we identified a partial open reading frame, which exhibited >60% sequence identity to human RoDH-4. The full-length cDNA for this enzyme was determined in our laboratory by 5'-RACE PCR and was found to be identical to the recently reported novel type of oxidative human 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Analysis of the genomic structure revealed that the gene for RoDH-like 3alpha-HSD has four translated exons and, possibly, a fifth exon that codes for the 5'-untranslated region. The gene for RoDH-4 appears to have only four exons. The positions of exon-intron boundaries and the sizes of the protein coding regions are identical in 3alpha-HSD and RoDH-4. Moreover, both genes are mapped to chromosome 12q13, and are located in a close proximity to each other. Both genes appear to have satellite pseudogenes. Thus, RoDH-4 and 3alpha-HSD genes share similar structural organization and cluster on human chromosome 12, near the gene for 11-cis retinol dehydrogenase.

A numerical model for magnetic induction tomographic measurements in biological tissues.

A finite-difference model has been developed for simulating measurements in magnetic induction tomography (MIT) for biological tissues. The model has three stages: (1) computation of the distribution of current induced in a volume of dielectric due to the magnetic field from an excitation coil; both the electrical conductivity and permittivity of the dielectric are taken into account: (2) computation of the e.m.f. induced in the sensing coil directly from the excitation coil; (3) computation of the e.m.f. induced in a sensing coil due to the current distribution in the dielectric. From the results of stages (2) and (3), the change in signal in the sensing coil due to the dielectric can be obtained, in magnitude and phase, as a fraction of the signal received in the absence of the dielectric. The peak values in the modelled curves agreed to within 14% of practical measurements at 10 MHz on volumes of saline solution with conductivities in the range 0.7 to 6 S m(-1).

Magnetic induction tomography. A measuring system for biological tissues.

A single-channel magnetic induction system operating at 10 MHz has been constructed. The system consists of an excitation coil and a sensing coil, between which different objects can be scanned. The eddy currents induced in the object cause perturbations in the sensed magnetic field, which are measured with a phase-sensitive detector with backing off of the signal to improve sensitivity. Scans were obtained for saline solutions with conductivities ranging from 0.001 to 6 Sm-1, encompassing the range for biological tissues. The imaginary part of the perturbation in the sensed magnetic field was found to be proportional to saline conductivity, consistent with theoretical prediction, and had a constant of proportionality of -1.2% per Sm-1. A filtered back-projection algorithm was used to generate tomographic images from the scans.

Effect of cellular retinol-binding protein on retinol oxidation by human class IV retinol/alcohol dehydrogenase and inhibition by ethanol.

All-trans retinoic acid (atRA) is a powerful morphogen synthesized in a variety of tissues. Oxidation of all-trans retinol to all-trans retinal determines the overall rate of atRA biosynthesis. This reaction is catalyzed by multiple dehydrogenases in vitro. In the cells, most all-trans retinol is bound to cellular retinol binding protein (CRBP). Whether retinoic acid is produced from the free or CRBP-bound retinol in vivo is not known. The current study investigated whether human medium-chain alcohol/retinol dehydrogenases (ADH) can oxidize the CRBP-bound retinol. The results of this study suggest that retinol bound to CRBP cannot be channeled to the active site of ADH. Thus, the contribution of ADH isozymes to retinoic acid biosynthesis will depend on the amount of free retinol in each cell. Physiological levels of ethanol will substantially inhibit the oxidation of free retinol by human ADHs: class I, alpha alpha and beta 2 beta 2; class II, pi pi; and class IV, sigma sigma.

A simple inexpensive device for monitoring patient respiration.

A simple device is described that monitors respiration by sounding an alarm if respiration ceases. It is light and portable and performs well, even in a 60 dB noise environment.

cDNA cloning and characterization of a new human microsomal NAD+-dependent dehydrogenase that oxidizes all-trans-retinol and 3alpha-hydroxysteroids.

We report the cDNA sequence and catalytic properties of a new member of the short chain dehydrogenase/reductase superfamily. The 1134-base pair cDNA isolated from the human liver cDNA library encodes a 317-amino acid protein, retinol dehydrogenase 4 (RoDH-4), which exhibits the strongest similarity with rat all-trans-retinol dehydrogenases RoDH-1, RoDH-2, and RoDH-3, and mouse cis-retinol/androgen dehydrogenase (

cDNA sequence and catalytic properties of a chick embryo alcohol dehydrogenase that oxidizes retinol and 3beta,5alpha-hydroxysteroids.

This study was undertaken to identify the cytosolic 40-kDa zinc-containing alcohol dehydrogenases that oxidize all-trans-retinol and steroid alcohols in fetal tissues. Degenerate oligonucleotide primers were used to amplify by polymerase chain reaction 500-base pair fragments of alcohol dehydrogenase cDNAs from chick embryo limb buds and heart. cDNA fragments that encode an unknown putative alcohol dehydrogenase as well as the class III alcohol dehydrogenase were identified. The new cDNA hybridized with two messages of approximately 2 and 3 kilobase pairs in the adult chicken liver but not in the adult heart, muscle, testis, or brain. The corresponding complete cDNA clones with a total length of 1390 base pairs were isolated from a chicken liver lambdagt11 cDNA library. The open reading frame encoded a 375-amino acid polypeptide that exhibited 67 and 68% sequence identity with chicken class I and III alcohol dehydrogenases, respectively, and had lower identity with mammalian class II (55-58%) and IV (62%) isozymes. Expression of the new cDNA in Escherichia coli yielded an active alcohol dehydrogenase (ADH-F) with subunit molecular mass of approximately 40 kDa. The specific activity of the recombinant enzyme, calculated from active site titration of NADH binding, was 3.4 min-1 for ethanol at pH 7.4 and 25 degrees C. ADH-F was stereospecific for the 3beta,5alpha- versus 3beta,5beta-hydroxysteroids. The Km value for ethanol at pH 7.4 was 17 mM compared with 56 microM for all-trans-retinol and 31 microM for epiandrosterone. Antiserum against ADH-F recognized corresponding protein in the chicken liver homogenate. We suggest that ADH-F represents a new class of alcohol dehydrogenase, class VII, based on its primary structure and catalytic properties.